Vaccines are used to induce specific immune responses against antigens, particularly against pathogen and tumor antigens. Adjuvants can be used to increase the humoral and/or cellular immune response to the antigen. With the aid of adjuvant, a smaller dose of antigen may be required to stimulate the immune response.
Adjuvants can be particulate adjuvants or non-particulate adjuvants. Particulate adjuvants can exist as microparticles in which the immunogen is incorporated into the microparticles. These microparticles may function by a depot mechanism, allowing slower clearance of the antigen from the injection site.
One example of a particulate adjuvant is an oil and water emulsion. For example, Freund's Complete Adjuvant is a water-in-oil emulsion composed of mineral oil mixed with killed Mycobacteria and an emulsifying agent. Incomplete Freund's Adjuvant lacks the mycobacterial components. Mineral oil in an emulsion can be replaced with metabolizable oil. U.S. Pat. Nos. 5,718,904 and 5,690,942.
ADDAVAX is a squalene-based oil-in-water emulsion used with vaccines. ADDAVAX is an adjuvant based on nano-emulsification of 2 components: sorbitan trioleate (0.5% w/v) in squalene oil (5% v/v) and TWEEN 80 (0.5% w/v) in sodium citrate buffer (10 mM, pH 6.5).
MONTANIDE™ ISA51 and ISA720 are adjuvants which allow the manufacture of water-in-oil emulsions. ISA51 is based on mineral oil (50/50 W/O) and ISA720 is based on nonmineral oil (30/70 W/O). They both contain mannide monooleate as an emulsifier.
U.S. Pat. No. 4,650,677 discusses the use of live, attenuated Aujesky virus, Infectious Bovine Rhinotracheitis virus, and Respiratory Syncytial Virus vaccines in oil-in-water emulsions for vaccination. This patent indicates there may be a protective action of the o/w-emulsion on the live virus against neutralization by the antibodies which are present in the animal.
Ganne et al., Vaccine 12:1190-1196 (1994) discusses the use of various oil and water emulsions with an adenoviral vector expressing a pseudorabies virus gp50 protein. Although Ganne et al. showed that one of the oil adjuvants combined with the adenovirus could increase anti-gp50 immune responses, the results demonstrated that free gp50 played a significant role in this response.
Kyriakis et al., Vaccine 27:2258-2264 (2009) gently mixed a vaccinia vector vaccine, NYVAC, with a solution of 20% adjuvant (oil-in-water emulsion) and 80% PBS prior to administration, and the immunogenicity was improved.
WO 2012/042279 discusses the use of MONTANIDE™ ISA720 in a two or three stage immunization regime in which a protein, an adenoviral vector expressing the protein, and a recombinant MVA vector expressing the protein were administered either separately, or in various combinations. The protein was used with MONTANIDE™ ISA720 adjuvant, including the recombinant MVA in combination with the purified protein with MONTANIDE™ ISA720. Thus, in this regime, the recombinant MVA with adjuvant additionally contained the recombinant protein encoded by the recombinant MVA. WO 2012/042279 did not show any effect of using MONTANIDE™ ISA720 with the recombinant MVA. Douglas et al., Vaccine 28:7167-7178 (2010) presented similar results.
Modified Vaccinia virus Ankara (MVA) has been administered to over 100,000 individuals during the smallpox eradication campaign without any complications. However, MVA still represents a complex mixture of viruses with different levels of attenuation and immunogenicity. Suter et al., Vaccine 27, 7442-7450 (2009). The plaque-purified MVA developed by Bavarian Nordic (MVA-BN) completely fails to replicate in mammals including humans and is safe even in immune-compromised hosts. Id. Besides its excellent safety profile, MVA is highly immunogenic in humans (Vollmar et al., Vaccine 24, 2065-2070 (2006)) and its efficacy has been proven in several smallpox animal models such as Ectromelia virus (ECTV), rabbitpox or monkeypox (Garza et al., Vaccine 27, 5496-5504 (2009); Samuelsson et al., J. Clin. Invest 118, 1776-1784 (2008); Stittelaar et al., J. Virol. 79, 7845-7851 (2005)). Another major advantage of MVA is its capacity to support the genetic insertion of several antigens (Timm et al., Vaccine 24, 4618-4621 (2006)) that could concomitantly induce protection against other infectious diseases or cancer ((Harrer et al. Antivir. Ther. 10, 285-300 (2005); Mandl et al., Cancer Immunol. Immunother. (2011); Meyer et al., Cancer Immunol. Immunother. 54, 453-467 (2005)). Vaccinia viruses have a cloning capacity of at least 25,000 bp of foreign DNA (Smith and Moss, Gene 25, 21-28 (1983)). Vaccinia virus can accommodate more than 29,000 bp as shown by cloning the cDNA of the complete genome of a feline coronavirus in vaccinia virus (Tekes et al., J. Virol. 82, 1851-1859 (2010)).
MVA is used for immunizations, frequently given in a prime and a boosting dose. Thus, a need in the art exists for compositions and methods for vaccination to achieve strong T-cell and/or antibody responses using a single dose and/or a smaller dose. The invention fulfills this need.